Effects of Orthosiphon grandiflorus, Hibiscus sabdariffa and Phyllanthus amarus extracts on risk factors for urinary calcium oxalate stones in rats.

PURPOSE: We evaluated the antilithic effect of Orthosiphon grandiflorus, Hibiscus sabdariffa and Phyllanthus amarus extracts on known risk factors for calcium oxalate stones in rats. MATERIALS AND METHODS: We divided 30 male Wistar rats into 5 equal groups. Controls were fed a standard diet and the remaining groups received a 3% glycolate diet for 4 weeks to induce hyperoxaluria. One glycolate fed group served as the untreated group and the others were given oral extracts of Orthosiphon grandiflorus, Hibiscus sabdariffa or Phyllanthus amarus at a dose of 3.5 mg daily. We collected 24-hour urine and blood samples. Kidneys were harvested for histological examination. We measured the renal tissue content of calcium and oxalate. RESULTS: The Hibiscus sabdariffa group showed significantly decreased serum oxalate and glycolate, and higher oxalate urinary excretion. The Phyllanthus amarus group showed significantly increased urinary citrate vs the untreated group. Histological examination revealed less CaOx crystal deposition in the kidneys of Hibiscus sabdariffa and Phyllanthus amarus treated rats than in untreated rats. Those rats also had significantly lower renal tissue calcium content than untreated rats. All parameters in the Orthosiphon grandiflorus treated group were comparable to those in the untreated group. CONCLUSIONS: Hibiscus sabdariffa and Phyllanthus amarus decreased calcium crystal deposition in the kidneys. The antilithic effect of Hibiscus sabdariffa may be related to decreased oxalate retention in the kidney and more excretion into urine while that of Phyllanthus amarus may depend on increased urinary citrate. In contrast, administering Orthosiphon grandiflorus had no antilithic effect.

Mechanisms by which a phytotherapeutic drug influences bladder activity in rats.

PURPOSE: We investigated the mechanisms by which Eviprostat, a phytotherapeutic drug for benign prostatic hyperplasia, influences bladder activity in rats. MATERIALS AND METHODS: A total of 42 female rats were divided into a control group and an Eviprostat group. Rats in the control group were fed a standard diet, while animals in the Eviprostat group were fed a diet containing 0.1% Eviprostat. After 2 weeks 14 rats (7 rats per group) underwent continuous cystometry with physiological saline or 0.1% acetic acid solution and bladder activity was recorded. Body weight, blood pressure, plasma monoamines and adenosine triphosphate were measured in another 14 rats (7 per group). In the remaining 14 rats (7 per group) 0.1% acetic acid solution was infused into the bladder and urinary adenosine triphosphate was measured before and after stimulation. RESULTS: During cystometry with acetic acid the interval between bladder contractions was shorter and maximum bladder contraction pressure was higher in the control group compared with results obtained using physiological saline but such differences were not seen in the Eviprostat group. Plasma adrenaline and noradrenaline were lower in the Eviprostat group than the control group but no difference in blood pressure was observed. Urinary adenosine triphosphate was higher in the 2 groups than before stimulation but the increase was smaller in the Eviprostat group than in the control group. CONCLUSIONS: These results suggest that Eviprostat acts to maintain low catecholamine and also inhibit pathological bladder activity by decreasing adenosine triphosphate release from the bladder.

Effect of Gosha-jinki-gan, a blended herbal medicine, on bladder activity in rats.

PURPOSE: We investigated the effect of the blended herbal medicine Gosha-jinki-gan on bladder activity and the autonomic nervous system in rats. MATERIALS AND METHODS: A total of 42 female rats were divided into a control diet group of 21 and a Gosha-jinki-gan diet group of 21. Rats in the control diet group were fed a standard diet, while animals in the Gosha-jinki-gan were fed a special diet containing 1.08% Gosha-jinki-gan (TJ107, Tsumura Co., Tokyo, Japan). After 4 weeks 28 rats, including 14 in the control and 14 in the Gosha-jinki-gan group, underwent continuous cystometry with physiological saline or 0.1% acetic acid solution and bladder activity was recorded. The remaining 14 rats were anesthetized with halothane, and body weight, serum amino acid (glutamate and glycine) and plasma monoamine (noradrenaline, adrenaline, dopamine and serotonin) levels were measured. RESULTS: The amplitude of bladder contraction on continuous cystometry with physiological saline was lower in the Gosha-jinki-gan diet group than in the control diet group, and plasma dopamine and serotonin levels were also lower in the Gosha-jinki-gan group. When cystometry was done with 0.1% acetic acid, the interval between bladder contractions was shortened in the control and Gosha-jinki-gan groups. However, the interval and duration of bladder contractions were longer in the Gosha-jinki-gan than in the control group. CONCLUSIONS: These results suggest that Gosha-jinki-gan inhibits bladder activity by maintaining the balance of the sympathetic and parasympathetic nervous systems at a low level.

[Sequential combined liver-kidney transplantation for a one-year-old boy with infantile primary hyperoxaluria type 1].

We present the case of a one-year-old male patient with infantile primary hyperoxaluria type 1 (PH1). The patient visited hospital because of growth delay and poor feeding when he was six months old, and was diagnosed as PH1 with chronic renal failure. He underwent peritoneal dialysis until receiving a living-related liver transplantation when he was seventeen months old, and after the operation, underwent hemodialysis or hemodiafiltration four times per week. Six months after the liver transplantation, his serum oxalate level decreased to around 20 micromol/l and a living-related kidney transplantation was successfully performed. Nine months have passed since the kidney transplantation, and the patient's liver and kidney functions have been good and his growth and development much better than before the sequential liver and kidney transplantation. However, his serum and urine oxalate levels remained high and he has required high dose hydration to prevent deposition of calcium oxalate crystals in his grafted kidney. The key-points for treating infantile PHI patients are summarized as follows; 1) make a precise diagnosis as soon as possible, 2) perform a combined liver-kidney transplantation successfully, 3) conduct careful monitoring of the serum and urine oxalate levels and continue adequate hydration after kidney transplantation until the serum and urine oxalate levels normalize. Furthermore, cooperation between the medical staff and the patient's family seems to be essential.

Intrathecal or dietary glycine inhibits bladder and urethral activity in rats with spinal cord injury.

PURPOSE: We examined the influence of intrathecal or dietary glycine on bladder and urethral activity in rats with spinal cord injury. MATERIALS AND METHODS: A total of 20 female Sprague-Dawley rats were used 4 weeks after lower thoracic spinal cord injury. The rats were divided into standard and 1% glycine diet groups. In the standard diet group isovolumetric cystometry and urethral pressure measurement were performed before and after intrathecal injection of glycine. In the 1% glycine diet group bladder and urethral activity were compared with control recordings in the standard diet group. RESULTS: In the standard diet group intrathecal injection of glycine prolonged the interval and decreased the amplitude of bladder contractions, decreased baseline urethral pressure and altered urethral activity during bladder contraction from a pattern of detrusor-sphincter dyssynergia to detrusor-sphincter synergy at 100 mug glycine. In the 1% glycine diet group the interval and amplitude of bladder contractions were prolonged and decreased, respectively, compared with those in the standard diet group. Baseline urethral pressure was lower than in the standard diet group even after intrathecal injection of 100 mug glycine. Urethral pressure did not change during bladder contraction and it was the same as baseline pressure. Residual urine volume was lower than in the standard diet group. CONCLUSIONS: Intrathecal or dietary glycine inhibits bladder and urethral activity, and improves detrusor hyperreflexia and detrusor-sphincter dyssynergia.

Urinary response to an oxalic acid load is influenced by the timing of calcium loading in rats.

PURPOSE: Dietary intake of calcium or dairy products has been shown to decrease urinary oxalate excretion by limiting its intestinal absorption. However, not enough attention has been given to whether there is any benefit from altering the schedule of ingesting calcium and oxalate. Therefore, we investigated the effects of changes in the timing of calcium and oxalate loading on urinary oxalate excretion. MATERIALS AND METHODS: Male Wistar rats weighing 180 to 200 gm were fasted and randomized into several groups. They were then administered normal saline or oxalic acid with or without calcium or milk. Calcium or milk was given immediately, or 5, 10, 15 or 30 minutes before or after the oxalate load. All treatments were given via gastrostomy. Urine samples were collected by bladder puncture just before administration and at hourly intervals up to 5 hours afterward. Urinary oxalate was measured by capillary electrophoresis. RESULTS: Urinary oxalate increased after the administration of oxalate alone, while it decreased when oxalate was combined with calcium or milk. Urinary oxalate showed a smaller increment when calcium or milk was given before than after oxalate loading, and it was much smaller when calcium or milk was given immediately before oxalate. CONCLUSIONS: Prior calcium loading appears to have a positive influence on decreasing oxalic acid absorption from the intestinal tract. Therefore, calcium or dairy products should always be ingested before a meal rich in oxalate to prevent oxalate absorption and decrease urinary oxalate excretion.

Major factors modulating the serum oxalic acid level in hemodialysis patients.

Ascorbic acid overload and vitamin B6 deficiency have been implicated in the development of hyperoxalemia in dialysis patients, but there is still disagreement about this. Hemodialysis patients who are exposed long-term hyperoxalemia may develop secondary oxalosis with an increased risk of cardiac, vascular, and bone disease, and thus may benefit from maintaining a low serum oxalic acid level. In 452 hemodialysis patients, the serum level of oxalic acid was 47.2 +/- 22.9 micromol /l before and 16.9 +/- 10.5 micromol/l after a 4-hour dialysis session, while the ascorbic acid levels were 39.0 +/- 92.7 micromol/l and 6.5 +/- 18.6 micromol/l, the glycolic acid levels were 7.3 +/- 10.1 micromol/l and 0.6 +/- 2.3 micromol/l, and the citric acid levels were 141.3 +/- 54.7 micromol/l and 117.6 +/- 37.2 micromol/l, respectively. Most patients (65.3 percent) had low serum ascorbic acid levels (less than 10 micromol/l) before hemodialysis. The serum level of oxalic acid [Ox] showed a significant positive correlation with the levels of ascorbic acid [AA], glycolic acid [Gly], and creatinine [Cre]: [Ox] = 21.711 + 0.181 x [AA] + 0.174 x [Gly] + 0.171 x [Cre], (all micromol/l, p less than 0.05). In 124 dialysis patients, the 4-pyridoxic acid level was 8.9 +/- 19.6 micromol /l before and 3.9 +/- 8.8 micromol/l after dialysis, and it was not correlated with oxalic acid or glycolic acid. Most dialysis patients (65.3 percent) had low serum levels of ascorbic acid, but a subgroup of patients (12 percent) had high serum ascorbic acid levels (more than 100 micromol/l) associated with hyperoxalemia (88.2 +/- 24.5 micromol/l). High-dose vitamin C supplementation may aggravate hyperoxalemia in hemodialysis patients, so attention should be paid to avoiding this risk.

Changes of bone remodeling immediately after parathyroidectomy for secondary hyperparathyroidism.

BACKGROUND: Successful parathyroidectomy for secondary hyperparathyroidism alleviates bone pain and is followed by the development of hypophosphatemia and hypocalcemia, as well as an increase in bone mineral density. An increase in osteoblast surface (Ob.S/BS) is not observed several months after surgery. In this study, we investigated early bone changes at 1 week after parathyroidectomy and the mechanism underlying an increase in bone mineral density. METHODS: Fourteen patients with severe secondary hyperparathyroidism underwent iliac bone biopsy before and 1 week after parathyroidectomy. Changes in histomorphometric parameters, including osteoclast surface (Oc.S/BS), eroded surface (ES/BS), erosion depth (E.De), fibrosis volume (Fb.V/TV), Ob.S/BS, osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid thickness (O.Th), were investigated. Changes in texture of mineralized bone and osteoid seams were also investigated. RESULTS: Oc.S/BS (P < 0.001), ES/BS (P < 0.01), and E.De (P < 0.001) decreased, but Fb.V/TV did not change at 1 week postoperatively. In particular, osteoclasts disappeared in almost all patients. Ob.S/BS (P < 0.001) increased, and cuboidal osteoblasts were proliferating on the trabecular surface where osteoclasts had existed before parathyroidectomy. As a result, newly developed osteoblasts coexisted with fibrous tissue after surgery. OV/BV (P < 0.005), OS/BS (P < 0.005), and O.Th (P < 0.005) increased, with lamellar osteoid volume showing a particular increase. Bone mineralization continued despite the low postoperative serum parathyroid hormone level. CONCLUSION: A rapid decrease in serum parathyroid hormone level after parathyroidectomy appears to suppress bone resorption, as well as cause a transient marked increase in bone formation and an increase in normal lamellar osteoid seams.

Urinary oxalic acid excretion differs after oral loading of rats with various oxalate salts.

BACKGROUND: To compare urinary oxalate excretion after the oral administration of oxalic acid, disodium oxalate, or calcium oxalate in rats. METHODS: Male Wistar rats were divided into four groups of six rats each and were intravenously hydrated with normal saline, and then were administered normal saline (control group), 10 mg of oxalic acid, equimolar disodium oxalate, or equimolar calcium oxalate via a gastrostomy. Urine specimens were collected just before administration and at hourly intervals up to 5 h afterwards. The urinary oxalate, calcium, magnesium and phosphorus levels were measured. RESULTS: Urinary oxalate excretion peaked at 1-2 h after administration of oxalic acid or equimolar disodium oxalate, while administration of calcium oxalate only caused a small increase of urinary oxalate excretion. Cumulative urinary oxalate excretion during 5 h was 1.69 +/- 0.10 mg (mean +/- SD; 17%), 1.43 +/- 0.13 mg (13%), and 0.22 +/- 0.03 mg (2%) after the administration of oxalic acid, disodium oxalate, and calcium oxalate, respectively. Urinary calcium excretion showed a decrease in the oxalic acid and disodium oxalate groups, while urinary magnesium or phosphorus excretion did not change significantly. CONCLUSION: The upper gastrointestinal tract seems to be the major site of oxalic acid absorption and only free oxalate is absorbed irrespective of whether it is the sodium salt or not. After binding to calcium in the gut, oxalic acid absorption seems to be inhibited in the presence of calcium and this means that calcium oxalate is poorly absorbed (at least in the upper gastrointestinal tract).